Pembrolizumab in Combination With Plinabulin and Docetaxel For Metastatic NSCLC After ICIs (KeyPemls-004)

NCT05599789 | Active Not Recruiting Phase 2

• 3 other identifiers: K2506BPI-2358-303MISP100168
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 2 Study of Pembrolizumab in Combination with Plinabulin and Docetaxel in previously treated Patients with Metastatic Non-Small Cell Lung Cancer and progressive disease (PD) after immunotherapy (Anti-PD-1/PD-L1 inhibitor) alone or in combination with Platinum-doublet Chemotherapy.

Conditions

Non Small Cell Lung Cancer Metastatic

Keywords

Carcinoma, Non-Small-Cell Lung; Pembrolizumab; Plinabulin; Docetaxel

Outcome Measures

Primary Outcomes (1)

• ORR, objective response rate

  the proportion of participants who have achieved a confirmed complete response (CR) or partial response (PR), which is assessed according to RECIST 1.1 criteria.

  through study completion, an average of 1 year

Secondary Outcomes (1)

• PFS, progression-free survival

  through study completion, an average of 1 year

Other Outcomes (3)

• OS, overall survival

  through study completion, an average of 1 year

• DOR, duration of response

  through study completion, an average of 1 year

• Adverse events (AEs)

  through study completion, an average of 1 year

Study Arms (1)

Pembrolizumab in Combination with Plinabulin and Docetaxel

EXPERIMENTAL

Pembrolizumab in Combination with Plinabulin and Docetaxel

Drug: Pembrolizumab in Combination with Plinabulin and Docetaxel

Interventions

Pembrolizumab in Combination with Plinabulin and Docetaxel DRUG

Pembrolizumab 200 mg Q3W IV infusion Day 1 of each 3-week cycle; Plinabulin 30 mg/m2 Q3W IV infusion Days 1 of each 3-week cycle; Docetaxel 75 mg/m² Q3W IV infusion Day 1 of each 3-week cycle.

Pembrolizumab in Combination with Plinabulin and Docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent histologically confirmed diagnosis of metastatic squamous or non-squamous NSCLC (AJCC Staging Manual, version 8) will be enrolled in this study.
• Male participants:
• A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period.
• A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 180 days after the last dose of study treatment.
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study drug.
• Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy or in combination with platinum-doublet chemotherapy.
• PD-1 treatment progression is defined by meeting all of the following criteria:
• Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
• Has demonstrated disease progression after anti-PD-1/L1 as defined by RECIST v1.1.
• Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb.
• Once disease progression is confirmed, the initial date of disease progression documentation will be considered the date of disease progression.
• Progression-free survival of ICIs treatment at least 6 months： PD after platinum doublet chemotherapy AND immunotherapy either sequentially or concomitantly for advanced NSCLC with negative driver gene mutations.
• If subjects have disease progression within six months of the last dose of chemotherapy for neoadjuvant/adjuvant ICIs in combination with platinum-doublet chemotherapy for resectable NSCLC, the ICIs combination treatment can be defined as first-line treatment.

You may not qualify if:

• Has received docetaxel or Plinabulin as monotherapy or in combination with other therapies.
• Has received other antitumor regimens before the initiation of the study regimen for those who had disease progression after prior ICI therapy.
• Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• Participants must have recovered from all AEs due to previous therapies to Grade 1 or less (except alopecia). Participants with ≤Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible.
• Major surgery, open biopsy, or obvious trauma within 4 weeks before enrollment.
• Has received prior radiotherapy within 2 weeks before the start of study intervention or has received lung radiation therapy \>30 Gy within 6 months before the first dose of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• History of hemorrhagic diarrhea, inflammatory bowel disease or active uncontrolled peptic ulcer disease. (Concomitant therapy with ranitidine or its equivalent and/or omeprazole or its equivalent is acceptable). History of ileus or other significant gastrointestinal disorder known to predispose to ileus or chronic bowel hypomotility.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression, clinically stable and without requirement of steroid treatment for at least 14 days prior to the first dose of study intervention.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab/ Plinabulin/Docetaxel and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• BeyondSpring Pharmaceuticals Inc.: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; NPI 2358; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Director of Department of Respiratory and Critical Care Medicine

Study Record Dates

• First Submitted: October 26, 2022
• First Posted: October 31, 2022
• Study Start: February 1, 2023
• Primary Completion: January 21, 2025
• Study Completion: December 31, 2025
• Last Updated: February 18, 2025

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)